Psilocybin for Depressive Disorders

383 papers and 145 clinical trials exploring psilocybin as a treatment for depressive disorders.

CompoundClassic Psychedelic

Psilocybin

Psilocybin is a naturally occurring tryptamine psychedelic that acts as a prodrug to psilocin, a potent 5-HT2A receptor agonist. It is the furthest advanced psychedelic in clinical development, with two positive Phase III trials in treatment-resistant depression and expanding regulated access in Australia, Germany, and US states.

Full Psilocybin profile

IndicationApproximately 260 million people worldwide are affected by depression.

Depressive Disorders

Depressive disorders, particularly major depressive disorder (MDD), are significant contributors to global mental health issues. Research into the therapeutic potential of psychedelics, such as psilocybin and ketamine, offers promising avenues for treatment, especially for cases that are resistant to conventional therapies.

Full Depressive Disorders profile

Safety summary

Psilocybin for Depressive Disorders: adverse events

Psilocybin safety reports for Depressive Disorders most often include headache, nausea, anxiety, fatigue among the source-backed named adverse events currently normalized in Blossom.

22 source papers|188 named AE rows|Top events: headache, nausea, anxiety

View adverse events

Dose summary

Psilocybin for Depressive Disorders: dose summaries

Psilocybin clinical studies for Depressive Disorders include 56 structured dose rows across 43 linked trials. Common source-reported dose patterns include 25 mg, 1 mg, 10 mg. Interpret these as descriptive trial protocols, not treatment recommendations.

113 source papers|56 dose rows|Patterns: 25 mg, 1 mg, 10 mg

View dosing

Academic Research

383 papers

Paywallindividual

Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial

This pilot trial (n=16) tested psilocybin-assisted cognitive behavioural therapy for adults with major depressive disorder, using 10 mg and 25 mg psilocybin doses alongside 12 therapy sessions. It was well accepted and feasible, with no serious adverse events, and most participants improved in depressive symptoms, with gains lasting three months after treatment.

Published: June 8, 2026
Journal: Journal of Affective Disorders
Authors: Weintraub, M. J., Jeffrey, J. K., Ichinose, M. C., Bergman, R. L., Shapiro, B., Barnett, G., Artin, H., Lynn, M., Salimian, A., Grody, S., Ramesh, R., Eales, L., Grob, C. S., Miklowitz, D. J.

Paywallindividual

Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression

This secondary analysis of an open-label trial (n=15) examined a single 25 mg dose of psilocybin with psychological support in veterans with treatment-resistant depression, focusing on anxiety, quality of life, functioning, and PTSD symptoms. Improvements were observed across these measures, but most were no longer significant after accounting for concurrent improvements in depression.

Published: June 4, 2026
Journal: Journal of Affective Disorders
Authors: Kelly, C. M., Fradet, M., Bostian, C. M., Donnelly, A., Ellis, S., Ostacher, M., Aaronson, S., Suppes, T.

Open Accessindividual

Real-World Psilocybin Therapy for Treatment-Resistant Depression: a Retrospective Observational Study

In a retrospective case series (n=19) of treatment‑resistant depression patients treated with psilocybin (20–35 mg) in routine clinical practice, depressive symptoms decreased significantly with large effect sizes on MADRS and BDI, though response and remission rates were lower than in controlled trials and no additive benefit of multiple doses was found.

Published: June 1, 2026
Journal: The Lancet Regional Health – Europe
Authors: Jungwirth, J., Westenhöfer, S., Aicher, H., Provaznikova, B., Kronenberg, G., Seifritz, E., Prinz, S., Olbrich, S.

Open Accessindividual

Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial

This naturalistic follow-up of a Phase IIb randomised active placebo-controlled trial (n=144) found that one or two 25 mg doses of psilocybin with psychotherapy were linked to sustained reductions in depression symptoms in treatment-resistant major depression (TRD) at six and twelve months. Benefits were similar across groups, while restarting antidepressant medication during follow-up was associated with worse scores.

Published: May 27, 2026
Journal: Psychotherapy and Psychosomatics
Authors: Mertens, L. J., Betzler, F., Brand, M., Evens, R., Jungaberle, A., Jungaberle, H., Kärtner, L., Majić, T., Schmitz, C. N., Ströhle, A., Scharf, D., Spangemacher, M., Wolff, M., Assadi, Z., Bahri, S., Becher, L., Färber, L. V., Harder, H., Kirchen, N., Kulakova, E., Kunz, L. C., Meijer, A., Rohrmoser, B., Wellek, S., Berger, M. M., Koslowski, M., Gründer, G.

Open Accessindividual

Psychedelic-assisted therapy: a survey on the clinical methods of Swiss physicians

This survey study (n=41) examined how Swiss physicians provide psychedelic-assisted therapy under legal exemptions, mainly for depression, anxiety, PTSD and chronic pain. It found wide variation in practice, with psilocybin, MDMA and LSD commonly used, music often played during sessions, and adverse effects usually including disorientation, feeling cold, anxiety and nausea.

Published: May 20, 2026
Journal: Therapeutic Advances in Psychopharmacology
Authors: Beichmann, K., Catzeflis, P., Aicher, H. D., Seragnoli, F., Calder, A., Amrani, A., Hasler, G.

Paywallindividual

From trials to clinics: investigators' perspectives on translating psychedelic research into clinical care

This qualitative study (n=21) interviewed US psychedelic clinical investigators about how treatments such as MDMA and psilocybin might move from trials into routine care. They saw major challenges in the role of psychotherapy, treatment cost and scalability, and the effects of hype and stigma on uptake.

Published: May 19, 2026
Authors: Mitchell, J., Neitzke-Spruill, L., Mathai, D. S., Robinson, J. O., Kavan, Z., Averil, L. A., McGuire, A. L.

Clinical Trials

145 trials

Not yet recruitingPhase II

Group PACBT for Depression

This Phase II, single-group trial (n=30) will assess group psilocybin-assisted cognitive behavioural therapy for adults with major depressive disorder, with a focus on acceptability and feasibility, while also exploring effects on depressive symptoms and psychosocial functioning. Participants aged 21 to 60 years with current or past major depressive episodes and active depressive symptoms will receive manualised group cognitive behavioural therapy alongside oral psilocybin. The intervention consists of 12 group PA-CBT sessions and two oral psilocybin administrations, given as a 10mg dose followed by a 25mg dose one month later, with all treatments delivered together in a group format. Primary outcomes include treatment acceptability from baseline to post-treatment, feasibility measured by participant retention, and change on the Hamilton Depression Rating Scale from baseline to the end of the study.

Started: January 1, 2027
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT07566104

Not yet recruitingPhase I/II

Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

This Phase I/Phase II, randomised, double-blind, quadruple-masked trial (n=50) will evaluate a single oral dose of psilocybin 5 mg, 10 mg or 25 mg, given alongside psychotherapy, in veterans and first responders with treatment-resistant depression (TRD) and co-occurring substance use disorder (SUD). The study will assess safety and tolerability, as well as whether psilocybin-assisted psychotherapy can reduce substance use severity and depressive symptoms. Participants will be assigned in parallel to one of three psilocybin dose groups and will complete two intake visits, three preparatory psychotherapy sessions, an 8 to 10 hour dosing session, and three weekly integrative psychotherapy sessions afterwards. Outcomes include adverse events, urine drug results, days of substance use, depression symptom ratings, plasma brain-derived neurotrophic factor (BDNF) during stress exposure, and resting brain functional connectivity on MRI, with repeated daily assessments across 6 weeks and follow-up through 12 weeks, including a 60-day follow-up.

Started: August 1, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07499583

Not yet recruitingPhase II

Anesthesia-Masked Psilocybin Therapy for Major Depression

This Phase II, randomised, double‑blind, crossover trial (n=10) will assess the safety, feasibility and effectiveness of masking psilocybin therapy with general anaesthesia in adults with major depressive disorder (age 25–65). Participants will receive oral psilocybin (10 mg and 25 mg) and placebo (0 mg) across repeated sessions administered under intravenous propofol anaesthesia so that both participants and outcome assessors remain blinded; the study will also collect preliminary data on changes in depressive symptoms. All participants complete four weekly dosing sessions (placebo, 10 mg, and two separate 25 mg sessions) in one of two counterbalanced sequences so every participant receives every dosing condition. Psilocybin or placebo capsules are given approximately 30 minutes before induction of general anaesthesia with propofol, with anaesthesia provided by a board‑certified anaesthesiologist at Stanford Hospital. Primary outcomes are blinding success measures (correct identification of psilocybin and accuracy of guessed dose) assessed 1 day after the final dosing session (Visit 21, Week 4); secondary data collection includes mood, sleep, wellbeing and anxiety questionnaires, optional consumer‑grade EEG sleep monitoring, and overall study duration per participant of about 7 weeks across ~25 visits.

Started: July 1, 2026
Type: interventional
Blinding: double
Randomized: Yes
Registry ID: NCT07479550

Not yet recruitingPhase I

Psilocybin as a Novel Therapy for Residual Anhedonia

This Phase I, randomised, triple-masked, parallel-group trial (n=90) will evaluate whether a single oral dose of psilocybin 25 mg can improve residual anhedonia and emotional blunting in adults with major depressive disorder who remain symptomatic despite ongoing SSRI or SNRI treatment. The study will compare psilocybin with placebo and will assess whether treatment can restore fronto-striatal reward circuit function and reduce anhedonia. Participants in both arms will complete six MRI sessions, with two scans before the administration day and four afterwards. The psilocybin group will receive a supervised one-time 25 mg capsule dose, while the control group will receive a matching placebo capsule containing 25 mg of inert filler. Key outcomes include change in Dimensional Anhedonia Rating Scale score and change in fronto-striatal connectivity (pgACC-NAcc functional connectivity) from baseline to end of study, with assessments planned from week -3 to week 8.

Started: July 1, 2026
Type: interventional
Blinding: triple
Randomized: Yes
Registry ID: NCT07607938

Not yet recruitingPhase III

Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression

This Phase III, randomised, quadruple‑masked, parallel trial (n=240) will evaluate the efficacy and risks of psilocybin for treatment‑resistant depression in U.S. military veterans with and without concurrent post‑traumatic stress disorder, with the primary outcome being change in the Montgomery‑Åsberg Depression Rating Scale (MADRS) at 2 weeks. This multi‑site study randomises participants to either a psilocybin intervention dose or a psilocybin comparator dose under blinded conditions. Consenting veterans will receive two psilocybin dosing sessions with psychological preparation, administration and integration support from a facilitator; participants are randomised at the first administration to one of the two doses and one month later all participants receive a 25 mg dose at the second session. Outcomes are measured by an independent evaluator masked to treatment at 2 and 4 weeks after each dosing session, with longer‑term follow‑up over 6 months, and both expected and unanticipated adverse events collected. Key eligibility includes English‑speaking U.S. veterans aged 18–75 years with a current major depressive episode (MADRS ≥20) who have not responded to ≥2 adequate antidepressant treatments.

Started: June 1, 2026
Type: interventional
Blinding: quadruple
Randomized: Yes
Registry ID: NCT07226232

Not yet recruitingPhase II

Group Retreat Psilocybin Therapy for Healthcare Clinicians With Loss of Meaning in Their Work and Symptoms of Depression

This Phase II, non-randomised, single-arm sequential dose-finding trial (n=72) will evaluate group retreat psilocybin therapy for healthcare clinicians with symptoms of depression and loss of meaning in their work. It will assess the feasibility, safety, and preliminary clinical effects of different preparation “doses” before a single psilocybin retreat session. Participants will be healthcare clinicians aged 25-70 years who are currently in clinical practice and have moderate or greater depressive symptoms. The study uses three sequential cohorts, each with 8 participants per retreat and 3 retreats per cohort, comparing 7 preparation sessions (6 virtual and 1 in-person), 4 preparation sessions (3 virtual and 1 in-person), and 2 preparation sessions (1 virtual and 1 in-person). The psilocybin dose depends on antidepressant use: 25 mg plus an optional 10 mg booster for those not taking an antidepressant, or 35 mg plus an optional 10 mg booster for those taking an antidepressant. The intervention includes preparation sessions, a single psilocybin session, and integration sessions, with outcomes collected at 1 week, 1 month, and 3 months after the retreat.

Started: June 1, 2026
Type: interventional
Blinding: none
Randomized: No
Registry ID: NCT07565909

Explore further

Search all Psilocybin papers Search all Depressive Disorders trials Full Psilocybin profile Full Depressive Disorders profile